Fluid purification system

ABSTRACT

Certain disclosed embodiments concern systems and methods of preparing dialysate for use in a home dialysis system that is compact and light-weight relative to existing systems and consumes relatively low amounts of energy. The method includes coupling a household water stream to a dialysis system; filtering the water stream; heating the water stream to at least about 138 degrees Celsius in a non-batch process to produce a heated water stream; maintaining the heated water stream at or above at least about 138 degrees Celsius for at least about two seconds; cooling the heated water stream to produce a cooled water stream; ultrafiltering the cooled water stream; and mixing dialysate components into the cooled water stream in a non-batch process.

CROSS REFERENCE TO RELATED APPLICATIONS

This is a divisional of U.S. patent application Ser. No. 16/138,441,filed Sep. 21, 2018, which is a divisional of U.S. patent applicationSer. No. 14/808,827, filed on Jul. 24, 2015, which is a continuation ofU.S. patent application Ser. No. 13/965,720, filed Aug. 13, 2013, nowissued as U.S. Pat. No. 9,138,687, which is a continuation of U.S.patent application Ser. No. 13/068,038, filed Apr. 29, 2011, now issuedas U.S. Pat. No. 8,524,086, which is a continuation of U.S. patentapplication Ser. No. 12/795,382, filed Jun. 7, 2010, now issued as U.S.Pat. No. 8,501,009. These prior applications are incorporated herein byreference in their entirety.

FIELD

The present disclosure concerns a fluid purification system,particularly a liquid purification system, and even more particularly asystem for preparing fluids for use in dialysis.

BACKGROUND

There are, at present, hundreds of thousands of patients in the UnitedStates with end-stage renal disease. Most of those require dialysis tosurvive. United States Renal Data System projects the number of patientsin the U.S. on dialysis will climb past 600,000 by 2012. Many patientsreceive dialysis treatment at a dialysis center, which can place ademanding, restrictive and tiring schedule on a patient. Patients whoreceive in-center dialysis typically must travel to the center at leastthree times a week and sit in a chair for 3 to 4 hours each time whiletoxins and excess fluids are filtered from their blood. After thetreatment, the patient must wait for the needle site to stop bleedingand blood pressure to return to normal, which requires even more timetaken away from other, more fulfilling activities in their daily lives.Moreover, in-center patients must follow an uncompromising schedule as atypical center treats three to five shifts of patients in the course ofa day. As a result, many people who dialyze three times a week complainof feeling exhausted for at least a few hours after a session.

Given the demanding nature of in-center dialysis, many patients haveturned to home dialysis as an option. Home dialysis provides the patientwith scheduling flexibility as it permits the patient to choosetreatment times to fit other activities, such as going to work or caringfor a family member. One requirement of a home dialysis system is areliable water purification system as dialysis requires purified waterfor mixing with a dialysate concentrate. Even trace amounts of mineralconcentrates and biological contamination in the water can have severeadverse effects on a dialysis patient. In addition, water purificationsystems in typical dialysis systems must be capable of purifying thevery large quantities of water required to run a full dialysis session.

Unfortunately, existing water purifications have drawbacks that limitpractical usage of such systems in a home dialysis system. Existingwater purification systems are large and bulky, often being as large asa residential washing machine and weighing over three hundred pounds.Such systems also very often consume large amounts of energy in order topurify relatively small amounts of water. In sum, existing waterpurification systems are bulky and expensive, making them practicallyunsuitable for use in the average patient's home.

SUMMARY

In view of the foregoing, there is a need for improved waterpurification systems that may be used in conjunction with home dialysis.Such a system would ideally be small, lightweight, portable, and havethe capability of reliably, reproducibly, highly efficiently andrelatively inexpensively providing a source of purified water ofsufficient volumes to enable home dialysis. In addition, such a waterpurification system could ideally be incorporated into a dialysis systemthat requires much less purified water at any one time than the volumestypically needed for dialysis today, thereby further reducing theexpense of running the system at home. In addition, the system would becapable of producing real-time, on-demand ultrapure water for dialysis,the gold standard of present-day dialysis. Disclosed herein is anin-line, non-batch water purification system that utilizes amicrofluidics heat exchanger for heating, purifying and cooling water.The system is compact and light-weight relative to existing systems andconsumes relatively low amounts of energy. The water purification systemis suitable for use in a home dialysis system although it can be used inother environments where water purification is desired. The system canalso be used to purify fluids other than water. The system can beconnected to a residential source of water (such as a running water tapto provide a continuous or semi-continuous household stream of water)and can produce real-time pasteurized water for use in home dialysis,without the need to heat and cool large, batched quantities of water.

In one aspect, disclosed is a method of preparing dialysate for use in adialysis system. The method includes coupling a water source, such as ahousehold water stream, to a dialysis system; filtering the waterstream; heating the water stream to at least about 138 degrees Celsiusin a non-batch process to produce a heated water stream; maintaining theheated water stream at or above at least about 138 degrees Celsius forat least about two seconds; cooling the heated water stream to produce acooled water stream; ultrafiltering the cooled water stream; and mixingdialysate components into the cooled water stream in a non-batchprocess.

In another aspect, disclosed is a method of preparing dialysate for usein a dialysis system that includes processing a household water streamin a non-batch process to produce an ultra-high-temperature-pasteurizedwater stream; and mixing dialysate components into saidultra-high-temperature-pasteurized water stream. The mixing of dialysatecomponents is performed in a non-batch process.

In another aspect, disclosed is a method of ultrapasteurizing a fluidincluding providing a microfluidic heat exchanger having a fluidflowpath for only a single fluid. The flowpath includes multiple fluidpathways for said single fluid to travel. The fluid flowpath includes aninlet portion, a heating portion and an outlet portion that thermallycommunicates with the inlet portion when the heat exchanger is inoperation. The method also includes introducing the fluid into the inletportion of the heat exchanger at a selected flow rate; transferring heatto the fluid in the inlet portion from the fluid in the outlet portion,thereby heating the fluid in the inlet portion and cooling the fluid inthe outlet portion; further heating the fluid in the heating portion toa temperature greater than about 130 degrees Celsius; maintaining thefluid at a temperature greater than about 130 degrees Celsius for aperiod of at least about two seconds at the selected flow rate; andcooling the fluid in the outlet portion at least in part by the transferof heat to the fluid in the inlet portion, and permitting the fluid toexit the microfluidic heat exchanger without interaction with a secondfluid within the heat exchanger.

In another aspect, disclosed is a fluid purification system including afluid pathway having an inlet where fluid flows into the system and anoutlet where fluid flows out of the system. The fluid pathway furtherincludes a first region where fluid flows in a first direction at afirst temperature; a heater region downstream of the first region; and asecond region downstream of the heater region where fluid flows in asecond direction at a temperature greater than the first temperature.The heater region includes at least one heater that transfers heat intofluid flowing through the heater region to increase the temperature offluid flowing in the heater region to a second temperature greater thanthe first temperature. Fluid flowing in the second region thermallycommunicates with fluid flowing in the first region such that heattransfers from fluid flowing in the second region to fluid flowing inthe first region resulting in a temperature reduction in the fluid as itflows through the second region. Fluid flows out of the pathway throughthe outlet at a temperature less than the second temperature.

Other features and advantages should be apparent from the followingdescription of various embodiments, which illustrate, by way of example,the principles of the disclosed devices and methods.

BRIEF DESCRIPTION OF THE DRAWINGS

FIG. 1 shows a high level, schematic view of a fluid purification systemadapted to purify a fluid such as a liquid.

FIG. 2 shows a schematic, plan view of an exemplary embodiment of amicrofluidic heat exchange system adapted to heat and cool a singlefluid without the use of a second fluid stream to add heat to or removeheat from the fluid.

FIG. 3A shows an exemplary embodiment of an inlet lamina that forms atleast one inlet pathway where fluid flows in an inward direction throughthe heat exchange system.

FIG. 3B shows an exemplary embodiment of an outlet lamina that forms atleast one outlet pathway where fluid flows in an outward directionthrough the heat exchange system.

FIG. 3C shows an exemplary embodiment having superimposed inlet andoutlet laminae.

FIG. 4 shows an enlarged view of an inlet region of the inlet lamina.

FIG. 5 shows an enlarged view of a heater region of the inlet lamina.

FIG. 6 shows an enlarged view of a residence chamber of both the inletlamina and outlet lamina.

FIG. 7A shows a plan view of another embodiment of an inlet lamina.

FIG. 7B shows a plan view another embodiment of an outlet lamina.

FIG. 8 shows a perspective view of an exemplary stack 805 of laminae.

FIG. 9 shows a perspective view of an example of an assembledmicrofluidic heat exchange system.

FIG. 10 shows a schematic view of an exemplary heater control systemcoupled to the microfluidic heat exchange system.

FIG. 11 shows a schematic, plan view of another exemplary embodiment offlow pathways for the microfluidic heat exchange system.

FIG. 12 shows a schematic, plan view of another exemplary embodiment offlow pathways for the microfluidic heat exchange system.

FIG. 13A shows another embodiment of an inlet lamina that forms an inletpathway where fluid flows in an inward direction through the heatexchange system.

FIG. 13B shows another embodiment of an outlet lamina that forms anoutlet pathway where fluid flows in an outward direction through theheat exchange system.

FIG. 14 is a table illustrating combinations of temperature and time toachieve various pasteurization levels.

DETAILED DESCRIPTION

In order to promote an understanding of the principals of thedisclosure, reference is made to the drawings and the embodimentsillustrated therein. Nevertheless, it will be understood that thedrawings are illustrative and no limitation of the scope of thedisclosure is thereby intended. Any such alterations and furthermodifications in the illustrated embodiments, and any such furtherapplications of the principles of the disclosure as illustrated hereinare contemplated as would normally occur to one of ordinary skill in theart.

FIG. 1 shows a high level, schematic view of a fluid purification systemadapted to purify a fluid such as a liquid. In an embodiment, the systemis adapted to be used for purifying water, such as water obtained from ahousehold tap, in a dialysis system and is sometimes described herein inthat context. However, it should be appreciated that the fluidpurification system can be used for purifying water in other types ofsystems and is not limited for use in a dialysis system. Also, thepurification system can be used to purify liquids other than water.

With reference to FIG. 1, the fluid purification system includes aplurality of subsystems and/or components each of which is schematicallyrepresented in FIG. 1. A fluid such as water enters the fluidpurification system at an entry location 105 and communicates with eachof the subsystems and components along a flow pathway toward an exitlocation 107. Upon exiting the fluid purification system, the fluid isin a purified state. This may include the fluid being in a pasteurizedstate although the fluid system does not necessarily pasteurize thefluid in all circumstances. The embodiment shown in FIG. 1 is exemplaryand not all of the components shown in FIG. 1 are necessarily includedin the system. The individual components included in the system may varydepending on the type and level of purification or pasteurizationrequired. The quantity and sequential order of the subsystems along theflow pathway shown in FIG. 1 is for purposes of example and it should beappreciated that variations are possible.

The fluid purification system includes at least one microfluidic heatexchange (HEX) system 110 adapted to achieve pasteurization of theliquid passing through the fluid purification system, as described morefully below. The fluid purification system may also include one or moreadditional purification subsystems, such as a sediment filter system115, a carbon filter system 120, a reverse osmosis system 125, anultrafilter system 130, an auxiliary heater system 135, a degassifiersystem 140, or any combination thereof. The fluid purification systemmay also include hardware and/or software to achieve and control fluidflow through the fluid purification system. The hardware may include oneor more pumps 150 or other devices for driving fluid through the system,as well as sensors for sensing characteristics of the fluid and fluidflow. The operation of the fluid purification system is described indetail below.

Microfluidic Heat Exchange System

FIG. 2 shows a schematic, plan view of an exemplary embodiment of themicrofluidic heat exchange system 110, which is configured to achievepasteurization of a liquid (such as water) flowing through the systemwithout the need for a second fluid stream to add heat to or remove heatfrom the liquid. FIG. 2 is schematic and it should be appreciated thatvariations in the actual configuration of the flow pathway, such as sizeand shape of the flow pathway, are possible.

As described more fully below, the microfluidic heat exchange systemdefines a fluid flow pathway that includes (1) at least one fluid inlet;(2) a heater region where incoming fluid is heated to a pasteurizationtemperature via at least one heater; (3) a residence chamber where fluidremains at or above the pasteurization temperature for a predeterminedtime period; (4) a heat exchange section where incoming fluid receivesheat from hotter (relative to the incoming fluid) outgoing fluid, andthe outgoing fluid cools as it transfers heat to the incoming fluid; and(5) a fluid outlet where outgoing fluid exits in a cooled, pasteurizedstate. Depending on the desired temperature of the outgoing fluid, oneor more additional heat exchanges may be required downstream to adjustthe actual temperature of the outgoing fluid to the desired temperaturefor use, for example, in dialysis. This is especially true in warmerclimates, where incoming water may be tens of degrees higher than watersupplied in colder climates, which will result in higher outlettemperatures than may be desired unless further cooling is applied. Inan embodiment, the flow pathway is at least partially formed of one ormore microchannels, although utilizing microfluidic flow fields asdisclosed in U.S. Provisional Patent Application No. 61/220,177, filedon Jun. 24, 2009, and its corresponding utility application entitled“Microfluidic Devices,” filed Jun. 7, 2010, and naming Richard B.Peterson, James R. Curtis, Hailei Wang, Robbie Ingram-Gobel, Luke W.Fisher and Anna E. Garrison, incorporated herein by reference, forportions of the fluid flow pathway such as the heat exchange section isalso within the scope of the invention. The relatively reduceddimensions of a microchannel enhance heat transfer rates of the heatexchange system by providing a reduced diffusional path length andamount of material between counterflow pathways in the system. In anembodiment, a microchannel has at least one dimension less than about1000 μm. The dimensions of a microchannel can vary and are generallyengineered to achieve desired heat transfer characteristics. Amicrochannel in the range of about 0.1 to about 1 mm in hydraulicdiameter generally achieves laminar fluid flow through the microchannel,particularly in a heat exchange region of the microchannel. The smallsize of a microchannel also permits the heat exchange system 110 to becompact and lightweight. In an embodiment, the microchannels are formedin one or more lamina that are arranged in a stacked configuration, asformed below.

The flow pathway of the microfluidic heat exchange system 110 may bearranged in a counterflow pathway configuration. That is, the flowpathway is arranged such that cooler, incoming fluid flows in thermalcommunication with hotter, outgoing fluid. The hotter, outgoing fluidtransfers thermal energy to the colder, incoming fluid to assist theheaters in heating the incoming fluid to the pasteurization temperature.This internal preheating of the incoming fluid to a temperature higherthan its temperature at the inlet 205 reduces the amount of energy usedby the heaters 220 to reach the desired peak temperature. In addition,the transfer of thermal energy from the outgoing fluid to the incomingfluid causes the previously heated, outgoing fluid to cool prior toexiting through the fluid outlet. Thus, the fluid is “cold” as it entersthe microfluidic heat exchange system 110, is then heated (first viaheat exchange and then via the heaters) as it passes through theinternal fluid pathway, and is “cold” once again as it exits themicrofluidic heat exchange system 110. In other words, the fluid entersthe microfluidic heat exchange system 110 at a first temperature and isheated (via heat exchange and via the heaters) to a second temperaturethat is greater than the first temperature. As the fluid follows an exitpathway, the fluid (at the second temperature) transfers heat toincoming fluid such that the fluid drops to a third temperature that islower than the second temperature and that is higher than the firsttemperature.

Exemplary embodiments of a fluid pathway and corresponding components ofthe microfluidic heat exchange system 110 are now described in moredetail with reference to FIG. 2, which depicts a bayonet-style heatexchanger, with the inlet and outlet on one side of the device, acentral heat exchange portion, and a heating section toward the oppositeend. The fluid enters the microfluidic heat exchange system 110 throughan inlet 205. In the illustrated embodiment, the flow pathway branchesinto one or more inflow microchannels 210 that are positioned in acounterflow arrangement with an outflow microchannel 215. As mentioned,microfluidic heat exchange system 110 may be formed by a stack oflayered lamina. The inflow microchannels 210 may be positioned inseparate layers with respect to the outflow microchannels 215 such thatinflow microchannels 210 are positioned above or below the outflowmicrochannels 215 in an interleaved fashion. In another embodiment, theinflow microchannels 210 and outflow microchannels 215 are positioned ona single layer.

The outflow microchannel 215 communicates with an outlet 207. In theillustrated embodiment, the inlet 205 and outlet 207 are positioned onthe same end of the microfluidic heat exchange system 110, although theinlet 205 and outlet 207 may also be positioned at different positionsrelative to one another.

The counterflow arrangement places the inflow microchannels 210 inthermal communication with the outflow microchannel 215. In this regard,fluid in the inflow microchannels 210 may flow along a directionalvector that is oriented about 180 degrees to a directional vector offluid flow in the outflow microchannels 215. The inflow and outflowmicrochannels may also be in a cross flow configuration wherein fluid inthe inflow microchannels 210 may flow along a directional vector that isoriented between about 180 degrees to about 90 degrees relative to adirectional vector of fluid flow in the outflow microchannels 215. Theorientation of the inflow microchannels relative to the outflowmicrochannels may vary in any matter that is configured to achieve thedesired degree of thermal communication between the inflow and outflowmicrochannels.

One or more heaters 220 are positioned in thermal communication with atleast the inflow microchannels 210 such that the heaters 220 can provideheat to fluid flowing in the system. The heaters 220 may be positionedinside the inflow microchannels 210 such that fluid must flow aroundmultiple sides of the heaters 220. Or, the heaters 220 may be positionedto the side of the inflow microchannels 210 such that fluid flows alongone side of the heaters 220. In any event, the heaters 220 transfer heatto the fluid sufficient to cause the temperature of the fluid to achievea desired temperature, which may include a pasteurization temperature inthe case of water to be purified. In an embodiment, the fluid is waterand the heaters 220 assist in heating the fluid to a temperature of atleast 100 degrees Celsius at standard atmospheric pressure. In anembodiment, the fluid is water and the heaters 220 assist in heating thefluid to a temperature of at least 120 degrees Celsius. In anembodiment, the fluid is water and the heaters 220 assist in heating thefluid to a temperature of at least 130 degrees Celsius. In anembodiment, the fluid is water and the heaters 220 assist in heating thefluid to a temperature of at least 138 degrees Celsius. In anotherembodiment, the fluid is water and is heated to a temperature in therange of about 138 degrees Celsius to about 150 degrees Celsius. Inanother embodiment, the fluid is heated to the highest temperaturepossible without achieving vaporization of the fluid.

Thus, the microfluidic heat exchange system 110 may maintain the fluidas a single phase liquid. Because water typically changes phases from aliquid into a gaseous state around 100 degrees Celsius, heating water tothe temperatures set forth above requires pressurization of the heatexchange system so that the single-phase liquid is maintainedthroughout. Pressures above the saturation pressure corresponding to thehighest temperature in the heat exchange system are sufficient tomaintain the fluid in a liquid state. As a margin of safety, thepressure is typically kept at 10 psi or higher above the saturationpressure. In an embodiment, the pressure of water in the microfluidicheat exchange system is maintained greater than 485 kPa to preventboiling of the water, and may be maintained significantly in excess ofthat level, such as 620 kPa or even as high as 900 kPa, in order toensure no boiling occurs. These pressures are maintained in the heatexchange system using a pump and a throttling valve. A pump upstream ofthe heat exchange system and a throttling valve downstream of the heatexchange system are used where the pump and throttling valve operate ina closed loop control setup (such as with sensors) to maintain thedesired pressure and flow rate throughout the heat exchange system.

Once the fluid has been heated to the pasteurization temperature, thefluid passes into a residence chamber 225 where the fluid remains heatedat or above the pasteurization temperature for a predetermined amount oftime, referred to as the “residence time”, or sometimes referred to asthe “dwell time”. In an embodiment, the dwell time can be less than orequal to one second, between one and two seconds, or at least about twoseconds depending on the flow path length and flow rate of the fluid.Higher temperatures are more effective at killing bacteria and shorterresidence times mean a more compact device. Ultrahigh temperaturepasteurization, that is designed to kill all Colony Forming Units (CFUs)of bacteria down to a concentration of less than 10⁻⁶ CFU/ml (such asfor purifying the water for use with infusible dialysate is defined tobe achieved when water is heated to a temperature of 138 degrees Celsiusto 150 degrees Celsius for a dwell time of at least about two seconds.Ultrapure dialysate has a bacterial load no greater than 0.1 CFU/ml.FIG. 14 indicates the required temperature and residence time to achievevarious levels of pasteurization. The heat exchange system describedherein is configured to achieve the various levels of pasteurizationshown in FIG. 14.

The fluid then flows from the residence chamber 225 to the outflowmicrochannel 215, where it flows toward the fluid outlet 207. Asmentioned, the outflow microchannel 215 is positioned in a counterflowrelationship with the inflow microchannel 210 and in thermalcommunication with the inflow microchannel 210. In this manner, outgoingfluid (flowing through the outflow microchannel 215) thermallycommunicates with the incoming fluid (flowing through the inflowmicrochannel 210). As the heated fluid flows through the outflowmicrochannel 215, thermal energy from the heated fluid transfers to thecooler fluid flowing through the adjacent inflow microchannel 210. Theexchange of thermal energy results in cooling of the fluid from itsresidence chamber temperature as it flows through the outflowmicrochannel 215. Moreover, the incoming fluid is preheated via the heatexchange as it flows through the inflow microchannel 210 prior toreaching the heaters 220. In an embodiment, the fluid in the outgoingmicrochannel 210 is cooled to a temperature that is no lower than thelowest possible temperature that precludes bacterial infestation of thefluid. When the heat exchange system pasteurizes the fluid, bacteria inthe fluid down to the desired level of purification are dead as thefluid exits the heat exchange system. In such a case, the temperature ofthe fluid after exiting the heat exchange system may be maintained atroom temperature before use in dialysis. In another embodiment, thefluid exiting the heat exchange system is cooled to a temperature at orbelow normal body temperature.

Although an embodiment is shown in FIG. 2 as having an outlet channelsandwiched between an inflow channel, other arrangements of the channelsare possible to achieve the desired degrees of heating and cooling andenergy requirements of the heaters. Common to all embodiments, however,is that all fluid pathways within the system are designed to be traveledby a single fluid, without the need for a second fluid to add heat to orremove heat from the single fluid. In other words, the single fluidrelies on itself, at various positions in the fluid pathway, to heat andcool itself.

The dimensions of the microfluidic heat exchange system 110 may vary. Inan embodiment, the microfluidic heat exchange system 110 is sufficientlysmall to be held in the hand of a user. In another embodiment, themicrofluidic heat exchange system 110 is a single body that weighs lessthan 5 pounds when dry. In another embodiment, the microfluidic heatexchange portion 350 of the overall system 110 has a volume of about onecubic inch. The dimensions of the microfluidic heat exchange system 110may be selected to achieve desired temperature and dwell timecharacteristics.

As mentioned, an embodiment of the microfluidic heat exchange system 110is made up of multiple laminar units stacked atop one another to formlayers of laminae. A desired microfluidic fluid flow path may be etchedinto the surface of each lamina such that, when the laminae are stackedatop one another, microfluidic channels or flow fields are formedbetween the lamina. Furthermore, both blind etching and through etchingmay be used for forming the channels in the laminae. In particular,through etching allows the fluid to change the plane of laminae and moveto other layers of the stack of laminae. This occurs in one embodimentat the outlet of the inflow laminae where the fluid enters the heatersection, as described below. Through etching allows all laminae aroundthe heater section to participate in heating of the fluid instead ofmaintaining the fluid only in the plane of the inlet laminae. Thisembodiment provides more surface area and lower overall fluid velocityto facilitate the heating of the fluid to the required temperature andultimately contributes to the efficiency of the device.

The microchannels or flow fields derived from blind and/or throughetching of the laminae form the fluid flow pathways. FIG. 3A shows aplan view of an exemplary embodiment of an inlet lamina 305 that formsat least one inlet pathway where fluid flows in an inward direction (asrepresented by arrows 307) through the heat exchange system 110.

FIG. 3B shows a plan view an exemplary embodiment of an outlet lamina310 that forms at least one outlet pathway where fluid flows in anoutward direction (as represented by arrows 312) through the heatexchange system 110. The inlet pathway and the outlet pathway may eachcomprise one or more microchannels. In an embodiment, the inlet andoutlet pathway comprise a plurality of microchannels arranged inparallel relationship.

FIGS. 3A and 3B show the lamina 305 and 310 positioned adjacent eachother, although in assembled device the lamina are stacked atop oneanother in an interleaved configuration. FIG. 3C shows the inlet lamina305 and outlet lamina 310 superimposed over one another showing both theinlet pathway and outlet pathway. The inlet lamina 305 and outlet lamina310 are stacked atop one another with a fluid conduit therebetween sofluid may flow through the conduit from the inlet pathway to the outletpathway, as described more fully below. When stacked, a transfer layermay be interposed between the inlet lamina 305 and the outlet lamina310. The transfer layer is configured to permit heat to transfer fromfluid in the outlet pathway to fluid in the inlet pathway. The transferlayer may be any material capable of conducting heat from one fluid toanother fluid at a sufficient rate for the desired application. Relevantfactors include, without limitation, the thermal conductivity of theheat transfer layer 110, the thickness of the heat transfer layer, andthe desired rate of heat transfer. Suitable materials include, withoutlimitation, metal, metal alloy, ceramic, polymer, or composites thereof.Suitable metals include, without limitation, stainless steel, iron,copper, aluminum, nickel, titanium, gold, silver, or tin, and alloys ofthese metals. Copper may be a particularly desirable material. Inanother embodiment, there is no transfer layer between the inlet andoutlet laminae and the laminae themselves serve as the thermal transferlayer between the flow pathways.

The inlet lamina 305 and outlet lamina 310 both include at least oneinlet opening 320 and at least one outlet opening 325. When the inletlamina 305 and outlet lamina 310 are stacked atop one another andproperly aligned, the inlet openings 320 align to collectively form afluid pathway that extends through the stack and communicates with theinlet pathway of the inlet laminae 305, as shown in FIG. 3C. Likewise,the outlet openings 325 also align to collectively form a fluid pathwaythat communicates with the outlet pathway of the outlet laminae 310. Anyquantity of inlet lamina and outlet lamina can be stacked to formmultiple layers of inlet and outlet pathways for the heat exchangesystem 110. The quantity of layers can be selected to providepredetermined characteristics to the microfluidic heat exchange system110, such as to vary the amount of heat exchange in the fluid, the flowrate of the fluid capable of being handled by the system, etc. In anembodiment, the heat exchange system 110 achieves incoming liquid flowrates of at least 100 ml/min.

In another embodiment, the heat exchange system 110 achieves incomingliquid flow rates of at least 1000 ml/min. Such a heat exchange systemmay be manufactured of a plurality of laminae in which the microfluidicpathways have been formed using a masking/chemical etching process. Thelaminae are then diffusion bonded in a stack, as described in moredetail below. In an embodiment, the stack includes 40-50 laminae with aflow rate of 2-3 ml/min occurring over each lamina. Higher flow ratescan be achieved by increasing the number of pairs of stacked laminaewithin the heat exchanger. In other embodiments, much higher flow ratescan be handled through the system.

In operation, fluid flows into the inlet pathway of the inlet lamina 305via the inlet opening 320. This is described in more detail withreference to FIG. 4, which shows an enlarged view of an inlet region ofthe inlet lamina 305. The inlet opening 320 communicates with an inletconduit 405 that guides the fluid to the inlet pathway. The inletopening 320 may configured with a predetermined size relative to thesize of the inlet conduit 405, which may have a diameter of 2-mm. Forexample, in an embodiment, the inlet opening 320 has an associatedhydraulic diameter that may be about ten to fifteen times larger thanthe hydraulic diameter of the inlet conduit 405. Such a ratio ofhydraulic diameters has been found to force fluid to distributerelatively evenly among the multiple inlet laminae. In anotherembodiment, for a 2-mm wide inlet flow path, a hydraulic diameter ratioof greater than 10:1, such as 15:1, may be used to ensure an evendistribution of fluid flow over the stack.

With reference still to FIG. 4, a downstream end of the inlet conduit405 opens into the inlet pathway, which flares outward in size relativeto the size of the inlet conduit 405. In this regard, one or more flowseparation guides, such as fins 410, may be positioned at the entrywayto the inlet pathway. The flow separation fins are sized and shaped toencourage an even distribution of fluid as the fluid flows into theinlet pathway from the inlet conduit 405. It should be appreciated thatthe size, shape, and contour of the inlet conduit 405 and inlet pathwaymay vary and that the embodiment shown in FIG. 4 is merely exemplary. Byway of example only, this region of the system could also comprise aflow field of pin-shaped members (of the sort disclosed in U.S.Provisional Patent Application No. 61/220,177, filed on Jun. 24, 2009,and its corresponding utility application entitled “MicrofluidicDevices”, filed Jun. 7, 2010, and naming Richard B. Peterson, James R.Curtis, Hailei Wang, Robbie Ingram-Gobel, Luke W. Fisher and Anna E.Garrison, incorporated herein by reference) around which the fluidflows.

With reference again to FIG. 3A, the inlet pathway and outlet pathwayeach include a heat exchange region. The heat exchange regions arereferred to collectively using the reference numeral 350 andindividually using reference numeral 350 a (for the inlet pathway) andreference numeral 350 b (for the outlet pathway). The heat exchangeregions 350 are the locations where the colder fluid (relative to thefluid in the outlet pathway) of the inlet pathway receives heattransferred from the hotter fluid (relative to the fluid in the inletpathway) of the outlet pathway. As discussed above, the relativelycolder fluid in the inflow pathway is positioned to flow in thermalcommunication with the relatively hotter fluid in the outflow pathway.In this layered embodiment, the inflow pathway is positioned immediatelyabove (or below) the outflow pathway when the lamina are stacked. Heattransfers across the transfer layer from the fluid in the outflowpathway to the fluid in the inflow pathway as a result of thetemperature differential between the fluid in the inflow pathway and thefluid in the outflow pathway and the thermal conductivity of thematerial separating the two pathways. Again rather than comprising aseries of microchannels, the heat exchange regions may also comprise amicrofluidic flow field as described above.

With reference still to FIG. 3A, the fluid in the inflow pathway flowsinto a heater region 355 from the heat exchange region 350. A pluralityof pins 357 may be positioned in the inlet flow pathway between the heatexchange region 350 and the heater region 355. The pins 357 disrupt thefluid flow and promote mixing, which may improve both fluid flow andheat distribution. FIG. 5 shows an enlarged view of the heater region355. In an embodiment, the inflow pathway bifurcates into at least twoflow pathways in the heater region 355 to accommodate a desired flowrate. Alternatively only one flow path through the heater region may beutilized, or three or more flow paths may be selected. The heater region355 includes one or more heaters 220 that thermally communicate withfluid flowing through this region, but are hermetically isolated fromthe flow path. The heaters 220 add heat to the incoming fluid sufficientto raise temperature of the fluid to the desired temperature, which mayinclude a pasteurization temperature. The incoming fluid was previouslypreheated as it flowed through the heat exchange region 350. Thisadvantageously reduced the energy requirements for the heaters.

The laminae in the stack may include through-etches at entry locations505 to the heater region 355 such that fluid entering the heater regioncan pass through all the laminae in the stack. Through etching allowsall laminae around the heater section to participate in heating of thefluid instead of maintaining the fluid only in the plane of the inletlaminae. This provides more surface area between the fluid and theheaters and also provides lower overall fluid velocity to facilitate theheating of the fluid to the required temperature.

As mentioned, the inflow pathway may bifurcate into multiple flowpathways. Each pathway may include one or more heaters 220 arrangedwithin the pathway so as to maximize or otherwise increase the amount ofsurface area contact between the heaters 220 and fluid flowing throughthe pathways. In this regard, the heaters 220 may be positioned towardsthe middle of the pathway such that the fluid must flow around eitherside of the heaters 220 along a semicircular or otherwise curvilinearpathway around the heaters 220. The heaters 220 can vary inconfiguration. In an embodiment, the heaters 220 are conventionalcartridge heaters with a ⅛-inch diameter which can be run in anembodiment at a combined rate of between about 70,000 and 110,000 W/m2,which results in energy usages of less than 100 W in one embodiment, andless than 200 W in another embodiment, for the entire stack running atabout 100 mL/minute. In an embodiment, the system uses six heaters in aconfiguration of three heaters per flow pathway wherein each heater usesabout 70 W for a 100 ml/min flow rate. In an embodiment the fluid isforced to flow around the heaters in paths 1.6 mm wide.

With reference again to FIG. 3A, the inflow pathway transitions from theheater section 355 to the residence chamber 360. By the time the fluidflows into the residence chamber 360, it has been heated to the desiredtemperature, such as the pasteurization temperature, as a result of theheat transfer in the heat exchange region 350 and/or by being heated inthe heater section 355. In the case of multiple laminae being stacked,the residence chamber 360 may be a single chamber that spans all of thelayers of laminae in the stack such that the fluid from each inletlamina flows into a single volume of fluid in the residence chamber 360.The residence chamber 360 is configured such that fluid flow ‘shortcuts’are eliminated, all of the fluid is forced to travel a flow pathway suchthat no portion of the fluid will reside in the residence chamber forthe less than the desired duration at a specified flow rate, and thefluid is maintained at or above the pasteurization temperature for theduration of the time (i.e., the dwell time) that the fluid is within theresidence chamber 360. In effect, the residence time is a result of thedimensions of the flowpath through the residence area and the flow rate.It will thus be apparent to one of skill in the art how to design aresidence pathway for a desired duration.

FIG. 6 shows an enlarged view of the region of the residence chamber 360for the inlet lamina 305 and outlet lamina 310. For clarity ofillustration, FIG. 6 shows the inlet lamina 305 and outlet lamina 310positioned side-by-side although in use the laminae are stacked atop oneanother such that the residence chambers align to form a residencechamber that spans upward along the stack. In an embodiment, theresidence chamber 360 incorporates a serpentine flow path as shown inthe enlarged view of the residence chamber of FIG. 6. The serpentineflow path provides a longer flow path to increase the likelihood of theliquid spending a sufficient amount of time within the residence chamber360.

After the fluid has reached the end of the serpentine flow path, itpasses (represented by arrow 610 in FIG. 6) to the outlet pathway of theoutlet lamina 310. With reference now to FIG. 3B, the outlet pathwaypasses between the heaters 220, which act as insulators for the fluid tolessen the likelihood of the fluid losing heat at this stage of the flowpathway. The heated fluid of the outlet pathway then flows toward theheat exchange region 350 b. The outlet flow pathway expands prior toreaching the heat exchange region 350 b. A set of expansion fans 367directs the fluid into the expanded heat exchange region 350 b of theoutlet pathway, where the fluid thermally communicates with the coolerfluid in the inflow pathway. As discussed, heat from the fluid in thehotter outflow pathway transfers to the cooler fluid in the inflowpathway. This results in cooling of the outflowing fluid and heating ofthe inflowing fluid. The fluid then flows from the heat exchange region350 b to the outlet opening 325. At this stage, the fluid is in acooled, pasteurized state.

In an embodiment, laminae having a thickness of 350 microns with anetch-depth of 175 microns, with 2.5-mm wide channels having a hydraulicdiameter of 327 microns were utilized. Each pair of laminae was able tohandle a fluid flow rate of approximately 3.3. mL/min of fluid, whichthus required 30 pairs of laminae in order to facilitate a flow of 100mL/min, with only a 15-mm long heat exchanger section. In an embodiment,the fluid flowpaths are designed in smooth, sweeping curves and aresubstantially symmetrically designed along the longitudinal axis of thestack; if the flow paths are not designed symmetrically, they aredesigned to minimize differences in the path line or lengths so as toevenly distribute the flow, the heating of the fluid and the variousdwell times.

The width of the ribs separating channels in the heat exchange portioncan be reduced, which would have the effect of increasing the availableheat transfer area and reducing the length of the heat exchange portionrequired for the desired energy efficiency level of the device. Energyefficiency levels of at least about 85%, and in some embodiment of atleast about 90% can be achieved, meaning that 90% of the thermal energyfrom the outgoing fluid can be transferred to the incoming fluid streamand recaptured without loss.

In this manner, a heat exchange system may be constructed to providepasteurized water continuously at a desired flow rate for real-timemixing of dialysate in a dialysis system, without the need either toheat, purify and store water in batched quantities or to provide bags ofpure water or of premixed dialysate for use by the patient.

FIG. 7A shows a plan view of another embodiment of an inlet lamina 705that forms at least one inlet pathway where fluid flows in an inwarddirection (as represented by arrows 707) through the heat exchangesystem 110. FIG. 7B shows a plan view another embodiment of an outletlamina 710 that forms at least one outlet pathway where fluid flows inan outward direction (as represented by arrows 712) through the heatexchange system 110. The flow pathway in this embodiment generallyfollows a different contour than the flow pathway of the embodiment ofFIGS. 3A and 3B. In actual use, the inlet lamina 705 and outlet lamina710 are stacked atop one another.

The fluid enters the inlet pathway of the inlet lamina 705 at an inlet720. The inlet pathway then splits into multiple pathways at the heatexchange region 750 a, which thermally communicates with a correspondingheat exchange region 750 b of the outlet lamina 710. In anotherembodiment, the inlet pathway does not split into multiple pathways butremains a single pathway. The inlet pathway could also be at leastpartially formed of one or more microfluidic flow fields as disclosed inU.S. Provisional Patent Application No. 61/220,177, filed on Jun. 24,2009, and its corresponding utility application entitled “MicrofluidicDevices”, filed Jun. 7, 2010, and naming Richard B. Peterson, James R.Curtis, Hailei Wang, Robbie Ingram-Gobel, Luke W. Fisher and Anna E.Garrison, incorporated herein by reference. After the heat exchangeregion 750 a, the inlet pathway transitions to an arc-shaped heaterregion 760 that thermally communicates with a heater 765, such as a150-Watt McMaster-Carr cartridge heater (model 3618K451). The heaterregion serves as both a region where the heater 765 heats the fluid andas a residence chamber where the fluid remains heated at or above thedesired temperature for a predetermined amount of time.

From the heater region 760 and residence chamber of the inlet lamina710, the fluid flows to the outlet lamina 710 at an entrance location770. The fluid then flows into the heat exchange region 750 b of theoutlet lamina 710, where the fluid transfers heat to the incoming fluidflowing through the heat exchange region 750 a of the inlet lamina 705.The fluid then exits the outlet lamina at an outlet 775. In embodiment,the lamina 705 and 710 are about 600 μm thick and the microfluidic flowpathways have a depth of about 400 μm to 600 μm. In each of theembodiments disclosed herein, the fluid flow path completely encircleseach of the heaters so that any shim material conducting heat away fromthe heater will have fluid flowing over it to receive the heat, therebyminimizing heat loss to the environment. In addition, ideally, theflowpaths around each heater will be relatively narrow so thatnon-uniform heating due to separation from the heaters will be avoided.

As mentioned, the microfluidic heat exchange system 110 may be formed ofa plurality of lamina stacked atop one another and diffusion bonded.Additional information concerning diffusion bonding is provided by U.S.patent application Ser. Nos. 11/897,998 and 12/238,404, which areincorporated herein by reference. In an embodiment, the stack includesmultiple sets of lamina with each set including an inlet lamina 305juxtaposed with an outlet lamina 310. Each set of juxtaposed inletlamina and outlet lamina forms a single heat exchange unit. The stack oflamina may therefore include a plurality of heat exchange units whereineach unit is formed of an inlet lamina 305 coupled to an outlet lamina310. The flow pathways for each lamina may be formed by etching on thesurface of the lamina, such as by etching on one side only of eachlamina. When the laminae are juxtaposed, the etched side of a laminaseals against the unetched sided of an adjacent, neighboring lamina.This may provide desirable conditions for heat exchange and separationof the incoming fluid (which is not pasteurized) and the outgoing fluid(which is pasteurized).

FIG. 8 shows a perspective view of an exemplary stack 805 of laminae.The stack 805 is shown in partial cross-section at various levels of thestack including at an upper-most outlet lamina 310, a mid-level inletlamina 305 a, and a lower level inlet lamina 305 b. As mentioned, thestack 805 is formed of alternating inlet lamina and outlet laminainterleaved with one another. The heaters 220 are positioned withincut-outs that extend through the entire stack 805 across all the laminaein the stack 805. The residence chamber 360 and the aligned inletopenings 320 and outlet openings 325 also extend entirely through thestack 805. The laminae may also include one or more holes 810 that alignwhen the lamina are stacked to form shafts through which alignment postsmay be inserted.

The quantity of laminae in the stack may be varied to accommodatedesired specifications for the microfluidic heat exchange system 110,such as the heating specifications. The heating specifications may bedependent on flow rate of fluid, heater power input, initial temperatureof incoming fluid, etc. In an embodiment, the stack 805 is less thanabout 100 mm long, less than about 50 mm wide at its widest dimension,and less than about 50 mm deep, with a volume of less than about 250cubic centimeters, although the dimensions may vary. In anotherembodiment, the stack 805 is about 82 mm long, about 32 mm wide at itswidest dimension, and about 26 mm deep, with a volume of about 69-70cubic centimeters, and a weight of about five pounds when dry, althoughthe dimensions may vary.

The lamina 305 and 310 may be any material capable of being patternedwith features useful for a particular application, such asmicrochannels. The thickness of the lamina may vary. For example, thelamina may have a thickness in the range of about 200 μm to about 100μm. In another embodiment, the lamina may have a thickness in the rangeof about 500 μm to about 100 μm. Some suitable lamina materials include,without limitation, polymers and metals. The lamina may be manufacturedof any diffusion bondable metal, including stainless steel, copper,titanium alloy, as well as diffusion bondable plastics. Because of theoperating pressures and temperatures involved, the need to avoidleaching of the lamina material into the heated fluid, such as water,and the desirability of multiple uses of this device before disposal, ithas been found that manufacturing the heat exchange system fromstainless steel, such as 316L stainless steel, has proven adequate,although other materials may be used as long as they withstand theoperating conditions without degradation.

The laminae are stacked in a manner that achieves proper alignment ofthe lamina. For example, when properly stacked, the inlet openings 320of all the lamina align to collectively form an inlet passage for fluidto flow into the system and the outlet openings 325 align tocollectively form an outlet passage, as shown in FIG. 8. Theproperly-aligned stack of lamina may also include one or more seats forcoupling the heaters 220 in the stack. One or more features can be usedto assist in proper alignment of the lamina in the stack, such asalignment posts and/or visual indicators of proper alignment. The stackmay include a top cover positioned on the top-most lamina and a bottomcover positioned on the bottom-most lamina. The stack may also includean external insulation wrap to prevent heat loss to the outsideenvironment.

FIG. 9 shows a perspective view of an example of an assembledmicrofluidic heat exchange system 110. The stack 805 of inlet/outletlaminae includes chemically etched upper and lower covers that seal thestack 805 against the atmosphere. These covers typically are thickerthan the laminae, and may be about 1 mm or more in thickness in anembodiment to withstand damage and the operating pressures necessary tomaintain the fluid in a single state. The cartridge heaters 220 aremounted in cavities that extend through the entire stack 805. A plate910 is secured (such as via bolts) to the stack and provides a means ofsecuring an inlet port 915 and an outlet port 920 to the stack 805. Theinlet port 915 and outlet port 920 can be piping having internal lumensthat communicate with the inlet openings 320 and outlet openings 325.

Before assembly of the stack, each hole of each lamina that is to accepta cartridge heater is designed slightly smaller than the diameter of thecartridge heater itself. After assembly of the entire stack, the hole isenlarged for a clearance fit between the hole inner diameter and thecartridge heater outer diameter, taking into account thermal expansionof the heater during operation, to provide a uniform surface for optimumheat transfer from the heater to the pasteurizer. This method avoids anypotential issues with misalignment of the shims if the holes in eachshim were to be properly sized to the cartridge heater prior toassembly.

A second plate 925 is also secured to the stack 805. The plate 925 isused to couple one or more elongated and sheathed thermocouples 930 tothe stack 805. The thermocouples 930 extend through the stack 805 andcommunicate with the laminae in the stack 805 in the region of the dwellchamber for monitoring fluid temperature in the dwell chamber. Thethermocouples that are to be inserted into solid sections of the stackutilize a slip fit for installation. The thermocouples that enter intothe fluid flow paths require a seal to prevent fluid leakage. In thesecases, the holes for accepting the thermocouples are generated after thestack is assembled by electrical discharge machining (EDM), because thistechnique generates very small debris that can easily be flushed out ofthe system, as compared with traditional drilling, which could result inlarger debris blocking some of the flow paths. Any of a variety ofsealing members, such as o-rings or gaskets, may be coupled to the stackto provide a sealed relationship with components attached to the stack,such as the plates 910 and 925, thermocouples 930, and inlet port 915and outlet port 920. It should be appreciated that the assembledmicrofluidic heat exchange system 110 shown in FIG. 9 is an example andthat other configurations are possible.

In an exemplary manufacture process, a stack of lamina is positioned ina fixture or casing and is then placed into a bonding machine, such as ahigh temperature vacuum-press oven or an inert gas furnace. The machinecreates a high temperature, high pressure environment that causes thelamina to physically bond to one another.

In an embodiment, the weight of the overall stack can be reduced byremoving some of the excess material from the sides of the stack,thereby eliminating the rectangular footprint in favor of a morematerial-efficient polygonal footprint.

FIG. 11 shows a schematic, plan view of another exemplary embodiment ofthe microfluidic heat exchange system 110. FIG. 11 is schematic and itshould be appreciated that variations in the actual configuration of theflow pathway, such as size and shape of the flow pathway, are possible.The embodiment of FIG. 11 includes a first flow pathway 1105 and asecond flow pathway 1110 separated by a transfer layer 1115. Fluidenters the first flow pathway at an inlet 1120 and exits at an outlet1125. Fluid enters the second flow pathway at an inlet 1130 and exits atan outlet 1135. The first and second flow pathways are arranged in acounterflow configuration such that fluid flows through the first flowpathway 1105 in a first direction and fluid flows through the secondflow pathway 1110 in a direction opposite the first direction. In thisregard, the inlet 1120 of the first flow pathway 1105 is located on thesame side of the device as the outlet 1135 of the second flow pathway1110. Likewise, the outlet 1125 of the first flow pathway 1105 islocated on the same side of the device as the inlet 1130 of the secondflow pathway 1110. The flow pathways may be least partially formed ofone or more microchannels, although utilizing microfluidic flow fieldsas disclosed in U.S. Provisional Patent Application No. 61/220,177,filed on Jun. 24, 2009, and its corresponding utility applicationentitled “Microfluidic Devices”, filed Jun. 7, 2010, and naming RichardB. Peterson, James R. Curtis, Hailei Wang, Robbie Ingram-Gobel, Luke W.Fisher and Anna E. Garrison, incorporated herein by reference, forportions of the fluid flow pathway is also within the scope of theinvention.

With reference still to FIG. 11, fluid enters the first flow pathway1120 at the inlet 1120 and passes through a heater region 1140. A heateris positioned in thermal communication with the heater region 1140 so asto input heat into the fluid passing through the heater region 1140.Prior to passing through the heater region 1140, the fluid passesthrough a heat exchange region 1145 that is in thermal communication(via the transfer layer 1115) with fluid flowing through the second flowpathway 1110. In an embodiment, the fluid flowing through the secondflow pathway 1110 is fluid that previously exited the first flow pathway1105 (via the outlet 1125) and was routed into the inlet 1125 of thesecond flow pathway 1110. As the previously-heated fluid flows throughthe second flow pathway 1110, thermal energy from the previously-heatedfluid in the second flow pathway 110 transfers to the fluid flowingthrough the first flow pathway 1120. In this manner, the fluid in thesecond flow pathway 1110 pre-heats the fluid in the heat exchange region1145 of the first flow pathway prior to the fluid reaching the heaterregion 1140.

In the heater region 1140, the heater provides sufficient thermal energyto heat the fluid to a desired temperature, which may be thepasteurization temperature of the fluid. From the heater region 1140,the fluid flows into a residence chamber 1150 where the fluid remainsheated at or above the desired temperature for the residence time. Thefluid desirably remains flowing, rather than stagnant, while in theresidence chamber 1150. From the residence chamber 1150, the fluid exitsthe first flow pathway 1105 through the outlet 1125 and is routed intothe inlet 1130 of the second flow pathway 1110.

The fluid then flows through the second flow pathway 1110 toward theoutlet 1135. As mentioned, the second flow pathway 1110 is in thermalcommunication with the first flow pathway 1105 at least at the heatexchange region 1145. In this manner, the previously-heated fluidflowing through the second flow pathway 1110 thermally communicates withthe fluid flowing through the first flow pathway 1105. As thepreviously-heated fluid flows through the second flow pathway 1110,thermal energy from the heated fluid transfers to the fluid flowingthrough the adjacent heat exchange region 1145 of the first flow pathway1105. The exchange of thermal energy results in cooling of the fluidfrom its residence chamber temperature as it flows through the secondflow pathway 1110. In an embodiment, the fluid in the second flowpathway 1110 is cooled to a temperature that is no lower than the lowestpossible temperature that precludes bacterial infestation of the fluid.

In another embodiment of the device of FIG. 11, the fluid flowing intothe second flow pathway 1110 is not fluid re-routed from the first flowpathway 1105 but is rather a separate fluid flow from the same sourceas, or from a different source than, the source for the first fluid flowpathway 1105. The fluid in the second flow pathway 1110 may or may notbe the same type of fluid in the first flow pathway 1105. For example,water may flow through both pathways; or water may flow through one flowpathway and a non-water fluid may flow through the other flow pathway.In this embodiment where a separate fluid flows through the secondpathway relative to the first pathway, the separate fluid has desirablybeen pre-heated in order to be able to transfer heat to the fluid in thefirst flow pathway 1105 at the heat exchange region 1145.

As in the previous embodiments, the embodiment of FIG. 11 may be made upof multiple laminar units stacked atop one another to form layers oflaminae. In addition, the embodiment of FIG. 11 may have the same orsimilar specifications as the other embodiments described herein,including materials, dimensions, residence times, and temperaturelevels.

In another embodiment shown in FIG. 12, a microfluidic heat exchangesystem 110 purifies a single fluid. FIG. 12 represents an exemplary flowpathway configuration for a single lamina. A plurality of such laminaemay be interleaved to form a stack of lamina as described above forother embodiments. The purification of the fluid may comprisepasteurizing the fluid although pasteurization is not necessary such aswhere the device is not used for dialysis. The heat exchange systemreceives a stream of incoming fluid 1205, which splits before enteringthe heat exchange system. A first portion of the stream of incomingfluid 1205 a enters at a first inlet 1210 a on one end of the system anda second portion of the stream of incoming fluid 1205 enters at a secondinlet 1205 b on the other, opposite end of the system. The two streamsof incoming fluid 1205 are distributed across the stacked laminae inalternating fashion such that there is no direct contact between the twofluid streams.

Each stream of incoming fluid 1205 enters a flow pathway 1207 and flowsalong the flow pathway toward an outlet 1215. One stream of fluid entersvia the inlet 1205 a and exits at an outlet 1215 a positioned on thesame end of the system as the inlet 1210 b, while the other stream offluid enters via the inlet 1205 b and exits at an outlet 1215 b on thesame end of the system as the inlet 1210 a. Each flow pathway 1207includes a first heat exchange region 1220 where heat is exchangedthrough a transfer layer between the incoming fluid and thepreviously-heated outgoing fluid flowing through a lamina immediatelyabove (or below) the instant lamina in the stack. As the fluid flowsthrough the heat exchange region 1220 it receives heat via the heattransfer and is pre-heated prior to entering a heater region 1225.

For each flow pathway 1207, the fluid then flows into the heater region1225, which thermally communicates with at least one heater, andpreferably multiple heaters, for communicating heat into the flowingfluid. The fluid is heated under pressure to a temperature at or abovethe desired threshold pasteurization temperature as described above forother embodiments. The heater region 1225 also serves as a residencechamber. The fluid flows through the residence chamber while held at orabove the desired temperature for the desired residence time. Thedesired residence time may be achieved, for example, by varying the flowrate and/or by employing a serpentine flow path of the required lengthwithin the heater region 1225. After leaving the heater region 1225, theoutgoing fluid enters a second heat exchange region 1230 where theoutgoing fluid exchanges heat with the incoming fluid flowing through alamina immediately above (or below) the instant lamina in the stack. Theoutgoing fluid then exits the flow pathways through the outlets 1210 aand 1210 b. The two streams of outgoing fluid then recombine into asingle stream of outgoing fluid 1235 before continuing on to theultrafilter to remove all or substantially all of the dead bacteriakilled by the pasteurization process.

FIG. 13A shows another embodiment of an inlet lamina that forms a spiralinlet pathway where fluid flows in an inward direction through the heatexchange system. FIG. 13B shows a corresponding outlet lamina that formsa similar spiral pathway where fluid flows in an outward direction. Aplurality of such inlet and outlet laminae may be interleaved to form astack of laminae as described above for other embodiments. The laminaeare shown having a circular outer contour although the outer shape mayvary as with the other embodiments.

With reference to FIG. 13A, the inlet lamina has a header forming aninlet 1305 where incoming fluid enters the inlet pathway. The inletpathway spirals inward toward a center of the pathway, where a heatingchamber 1310 is located. The heating chamber 1310 also serves as aresidence chamber for the fluid, as described below. One or more heatersare positioned in thermal communication with the heating chamber 1310 toprovide heat to fluid flowing in the heating chamber 1310. The heatingchamber 1310 extends across multiple laminae in the stack and includes aconduit that communicates with the outlet lamina shown in FIG. 13B. Thefluid enters the outlet lamina from the heating chamber 1310. The outletlamina has an outflow pathway that spirals outward from the heatingchamber 1310 toward an outlet 1320.

In use, the fluid enters the inlet pathway of the inlet lamina throughthe inlet 1305 shown in FIG. 13B. The fluid then flows along the spiralinlet pathway toward the heater chamber 1310. As in the previousembodiments, the incoming fluid is at a temperature that is less thanthe previously-heated fluid flowing through the outlet lamina, which ispositioned immediately above or below the inlet lamina. As the fluidflows through the inlet pathway, the fluid receives heat from thepreviously-heated fluid flowing through the outlet pathway of the outletlamina. This serves to pre-heat the fluid prior to the fluid flowinginto the heating chamber 1310. The fluid then flows into the heatingchamber 1310 where the fluid receives heat from the one or more heaters.

While in the heating chamber 1310, the fluid is heated under pressure toa temperature at or above the desired threshold pasteurizationtemperature as described above for other embodiments. As mentioned, theheating chamber 1310 also serves as a residence chamber. The fluid flowsthrough the residence chamber while held at or above the desiredtemperature for the desired residence time. As in other embodiments, thedesired residence time may be achieved, for example, by varying the flowrate and/or by employing a serpentine flow path of the required lengthwithin the heater chamber 1310. After leaving the heater chamber, theoutgoing fluid enters the outlet pathway of an outlet lamina such asshown in FIG. 13B. The outgoing fluid flows outward from the heatingchamber 1310 along the spiral flow pathway toward the outlet 1320. Thespiral pathway of the inlet lamina thermally communicates with thespiral pathway of the outlet lamina across a transfer layer As theoutgoing fluid flows along the spiral pathway, it exchanges heat withthe incoming fluid flowing through an inlet lamina immediately above (orbelow) the instant lamina in the stack. The outgoing fluid then exitsthe stack of lamina via the outlet 1320 before continuing on to theultrafilter to remove all or substantially all of the dead bacteriakilled by the pasteurization process.

Control System

The microfluidic heat exchange system 110 may include or may be coupledto a control system adapted to regulate and/or control one or moreaspects of the fluid flow through the system, such as fluid flow rate,temperature and/or pressure of the fluid, chemical concentration of thefluid, etc. FIG. 10 shows a schematic view of an exemplary heatercontrol system 805 communicatively coupled to the microfluidic heatexchange system 110. The heater control system 1005 includes at leastone power supply 1015 communicatively coupled to a heater control unit1020, which communicates with a control logic unit 1025. The heatercontrol unit 1020 is adapted to control the power supply to the heaters,either on an individual basis or collectively to a group of heaters.This permits temporal and spatial control of heat supplied to themicrofluidic heat exchange system 110.

The heater control system 1005 may include one or more temperaturesensors 1010 positioned in or around the microfluidic heat exchangesystem 110 for sensing fluid temperature at one or more locations withinthe fluid flow path. The type of sensor can vary. In an embodiment, oneor more thermocouples are used as the sensors 1010. The sensors 1010communicate with the heater control unit 1020 and the control logic unit1025 to provide a temperature feedback loop. The heater control system1005 provides for feedback control of fluid temperature in the system toensure, for example, that fluid is being heated to the requiredpasteurization temperature and/or that the fluid is not overheated orunderheated. For example, the heater control unit 1020 in conjunctionwith the control logic unit 1025 may adjust power to one or more of theheaters based on a sensed temperature in order to achieve a desiredtemperature profile in one or more locations of the fluid flow path. Theheater control system 1005 may include other types of sensors such as,for example, pressure sensors, flow rate sensors, etc. to monitor andadjust other parameters of the fluid as desired.

The heater control system 1005 may also be configured to provide one ormore alarms, such as a visual and/or audio indication and/or atelecommunications signal, to the user or a remote monitor of systemfunctions to inform such parties when the temperature is at an undesiredlevel. For example, the control unit 1020 may comprise one or moretemperature set limits within which to maintain, for example, theresidence chamber temperature. If a limit is exceeded—i.e., if thetemperature falls below the lower operating limit or above the upperoperating limit, the control system may bypass the heater, set off analarm and cease operation of the overall water purification system untilthe problem can be diagnosed and fixed by the operator. In this regard,the control system 1005 may include a reporting unit 1030 that includesa database. The reporting unit 1005 is configured to log and store datafrom the sensors and to communicate such data to a user or monitor ofthe system at a remote site.

Exemplary Fluid Purification Procedure

With reference again to FIG. 1, an exemplary configuration for purifyingfluid using the fluid purification system is now described including adescription of a fluid flow path through the system. It should beappreciated that the description is for example and that variations tothe flow path as well as to the arrangement of the subsystems andhardware are possible. The fluid purification system is described in anexemplary context of being a component of a dialysis system. In thisexample, the fluid purification system is used to purify water that isused by the dialysis system. The fluid purification system is notlimited to use for purifying water in dialysis systems.

As shown in FIG. 1, water enters the system via an entry location 105,flows along a flow pathway, and exits the system via an exit location107. The flow pathway may be formed by any type of fluid conduit, suchas piping. The piping may include one or more sample ports that provideaccess to water flowing through the piping. One or more subsystems,including the microfluidic heat exchange system 110, are positionedalong the pathway for processing the water prior to the water exitingthe system. As mentioned, the subsystems may include, for example, asediment filter system 115, a carbon filter system 120, a reverseosmosis system 125, an ultrafilter system 130, an auxiliary heatersystem 135, a degassifier system 140, or any combination thereof.

The fluid purification system may also include hardware and/or softwareto achieve and control fluid flow through the fluid purification system.The hardware may include one or more pumps 150 and a throttling valve orother devices for driving fluid through the system, as well as sensorsfor sensing characteristics of the fluid and fluid flow, such as flowsensors, conductivity sensors, pressure sensors, etc. The hardware maycommunicate with a control system that controls operation of thehardware.

Upon entering the system, the water flows through at least one sedimentfilter system 115, which includes one or more sediment filters thatfilter sediment from the water flowing therethrough. The water thenflows through a carbon filter system 120, which includes one or morecarbon filters that filter organic chemicals, chlorine and chloraminesin particular from the water. One or more pumps may be positioned atvarious locations along the water flow pathway such as between thefilter subsystems. In addition, a conductivity sensor may be coupled tothe pathway downstream of the carbon filter system 120 and downstream ofthe reverse osmosis system to determine the percentage of dissolvessolids removed. The water flows from the carbon filter system 120 to areverse osmosis system 125 configured to remove particles from the waterpursuant a reverse osmosis procedure. The sediment filter 115 removesparticulate matter down to 5 microns or even 1 micron. The carbon filter120 removes chlorine compounds. The reverse osmosis system 125 usuallyremoves greater than 95% of the total dissolved solids from the water.

The sediment filter system 115, carbon filter system 120, and reverseosmosis system 125 collectively form a pre-processing stage that removesa majority of dissolved solids, bacteria contamination, and chemicalcontamination, if any, from the water. The water is therefore in asomewhat macro-purified state prior to reaching the heat exchange system110. Thus, the preprocessing stage supplies relatively clean water tothe downstream pumps and also to the heat exchange system 110. Thisreduces or eliminates the potential for scale build-up and corrosionduring heating of the water by the heat exchange system 110.

After the water passes the pre-processing stage, a pump 150 may be usedto increase the water pressure to a level higher than the saturationpressure encountered in the heat exchange system 110. This would preventphase change of the water inside the heat exchange system 110. Thus, ifthe highest temperature reached in the heat exchange system 110 is 150degrees Celsius where the water would have a saturation pressure of 475kPa (approximately 4.7 atmospheres or 69 psia), the pressure of thewater coming out of the pump would exceed the saturation pressure. Thepump desirably increases the water pressure to a level that is at orexceeds the saturation pressure to ensure no localized boiling. This canbe important where the heat exchange system is used to pasteurize waterand the water is exposed to high temperatures that may be greater than138 degrees Celsius, i.e., well above the boiling point of water atatmospheric pressure.

The water, which is now pressurized above, or significantly above, thesaturation pressure, enters the heat exchange system 110, whichpasteurizes the water as described in detail above. The heat exchangesystem 110 may be encased in insulation to reduce the likelihood of heatloss of the water passing therethrough. After leaving the heat exchangesystem 110, the water passes into a throttling valve 160, whichmaintains the pressure though the water path from the pump 150 to outletof the heat exchange system 110. The throttling valve 160 and the pump150 may be controlled and adjusted to achieve a flow rate and a desiredpressure configuration. The pump 150 and the throttling valve 160 maycommunicate with one another in a closed loop system to ensure therequired pressure is maintained for the desired flow rate andtemperature. A degassifier system 140 may also be incorporated into theflow path for removing entrained gas from the water.

After the water leaves the throttling valve 160, it passes to anultrafilter system 130 that removes macromolecules and all orsubstantially all of the dead bacteria killed by the pasteurizationprocess from the water to ensure no endotoxins remain in the waterbefore mixing the dialysate. Where the water is used in a dialysissystem, the presence of macromolecules may be detrimental to thedialysis process. The water then passes through a heater system that mayheat the water to a desired temperature, such as to normal bodytemperature (98.6 degrees Fahrenheit). Where the water is used fordialysis, the water is then passed to a mixer 170 that mixes the cleanwater with a supply of concentrate solutions in order to make dialysate.

Startup and Shutdown of Fluid Purification System

Where the fluid purification system is used for dialysis, it isimportant to avoid bacterial contamination of the fluid flow path, bothwithin the heat exchanger system 110 and throughout the componentsdownstream of the heat exchanger system 110. In this regard, the heatexchanger system 110, which serves as a pasteurizer, is desirablyoperated in a manner that ensures clean fluid flow upon startup of thefluid purification system and also avoids bacterial contamination of thedownstream components, or at least mitigates the contamination effects,upon shut down (i.e., when the heaters 220 are de-powered).

In an embodiment, clean fluid flow upon startup is achieved by initiallyflowing a sterilizing liquid through the heat exchanger system 110 whilethe heaters 220 are being powered up. The sterilizing liquid then flowsthrough all the components downstream of the heat exchanger system 110until the heat exchanger system 110 attains a desired operatingtemperature. Upon the heat exchanger system 110 reaching the desiredoperating temperature, fluid flow to the heat exchanger system 110switches to water from the reverse osmosis system 125. The water passesthrough the heat exchanger system 110 (which has achieved the desiredoperating temperature) to flush the sterilizing liquid out of the flowpathway of the heat exchanger system 110. Various sterilizing solutionsmay be used. The solution, for example, can be a 1% chlorine in watermixture, or some other widely recognized water additive that can killbacteria.

The fluid purification system may be shut down as follows. The heaters220 are de-powered while fluid flow through the heat exchanger system110 is maintained. Alternatively, a sterilizing liquid may be flowedthrough the heat exchanger system 110 until the heat exchanger system110 attains near room temperature conditions. In this manner, the flowpathway is maintained in a sterilized condition as the heat exchangersystem 110 shuts down. The flow pathway of the heat exchanger system 110is then closed or “locked down” with sterilizing liquid present in theflow pathway of the heat exchanger system 110. The presence of thesterilizing liquid greatly reduces the likelihood of bacterialcontamination during shutdown.

In another embodiment, one or more valves are positioned in the flowpathway of fluid purification system wherein the valves allow acirculating flow of solution to loop through the pump 150, heatexchanger system 110, and downstream components in a recirculation loopuntil desired pasteurization conditions are achieved during startup. Thevalves are then set to allow the sterilizing liquid to be flushed fromthe system. An auxiliary component, such as a microchannel fluid heater(without heat exchange capability), can also be incorporated to providethe ability to circulated a warmed (e.g., less than 100 degrees Celsius)sterilizing liquid through the downstream components and/or through theunpowered heat exchanger system 110. The sterilizing liquid can be usedduring either a start-up or shut-down process for keeping the flowpathway and components clean over the span of weeks and/or months. Theuse of a recirculation loop for sterilizing liquid at start up isanother manner to prevent bacteria from entering the fluid purificationsystem before the heat exchanger system 110 achieves operatingtemperatures. A timing control logic may be used with a temperaturesensing capability to implement a process that ensures quality controlover the start-up and shut down processes. The control logic may beconfigured to initiate flow only after the heat exchanger system 110 ora heater attains a preset temperature.

The flow path may include one or more bypass circulation routes thatpermit circulation of cleaning and/or sterilization fluid through theflow path. The circulation route may be an open flow loop wherein fluidflowing through the circulation route is dischargeable from the systemafter use. In another embodiment, the circulation route may be a closedflow loop wherein fluid flowing the circulation route not dischargeablefrom the system. Alternately, the system may include both open andclosed circulation routes.

The present specification is related to subject matter disclosed in U.S.Pat. No. 8,753,515 entitled “Dialysis System with UltrafiltrationControl,” filed on Jun. 7, 2010, naming James R. Curtis, Ladislaus F.Nonn, and Julie Wrazel, and U.S. Pat. No. 8,801,922, entitled “DialysisSystem,” filed on Jun. 7, 2010, naming Julie Wrazel, James R. Curtis,Ladislaus F. Nonn, Richard B. Peterson, Hailei Wang, RobbieIngram-Goble, Luke W. Fisher, Anna B. Garrision, M. Kevin Drost, GoranJovanovic, Richard Todd Miller, Bruce Johnson, Alana Warner-Tuhy andEric K. Anderson, which are incorporated herein by reference in theirentirety.

While this specification contains many specifics, these should not beconstrued as limitations on the scope of an invention that is claimed orof what may be claimed, but rather as descriptions of features specificto particular embodiments. Certain features that are described in thisspecification in the context of separate embodiments can also beimplemented in combination in a single embodiment. Conversely, variousfeatures that are described in the context of a single embodiment canalso be implemented in multiple embodiments separately or in anysuitable sub-combination. Moreover, although features may be describedabove as acting in certain combinations and even initially claimed assuch, one or more features from a claimed combination can in some casesbe excised from the combination, and the claimed combination may bedirected to a sub-combination or a variation of a sub-combination.Similarly, while operations are depicted in the drawings in a particularorder, this should not be understood as requiring that such operationsbe performed in the particular order shown or in sequential order, orthat all illustrated operations be performed, to achieve desirableresults.

Although embodiments of various methods and devices are described hereinin detail with reference to certain versions, it should be appreciatedthat other versions, embodiments, methods of use, and combinationsthereof are also possible. Therefore the spirit and scope of theappended claims should not be limited to the description of theembodiments contained herein.

We claim:
 1. A fluid purification system comprising: a pump adapted topump household water through a pump outlet; a microfluidic heatexchanger downstream of the pump and coupled to the fluid flow pathway,the microfluidic heat exchanger comprising an inlet in fluidcommunication with the pump outlet, an inflow microchannel downstream ofthe inlet, a heater downstream of the inflow microchannel, an outflowmicrochannel downstream of the heater and in thermal communication withthe inflow microchannel to permit heat transfer between water flowing inthe outflow microchannel and water flowing in the inflow microchannel,the microfluidic heat exchanger being configured to heat the water to apasteurization temperature, maintain the water at the pasteurizationtemperature for a period of time effective to pasteurize the water, andcool the pasteurized water to a temperature lower than thepasteurization temperature; and a mixer downstream of the microfluidicheat exchanger, the mixer comprising dialysate components for additionto water flowing from the microfluidic heat exchanger.
 2. The system ofclaim 1 wherein the microfluidic heat exchanger further comprises aplurality of inflow microchannels in fluid communication with the inletand a plurality of outflow microchannels in fluid communication with themixer.
 3. The system of claim 2 wherein the microchannels are disposedin a plurality of stacked laminae.
 4. The system of claim 3 wherein theinflow microchannels and the outflow microchannels are separated by thelaminae.
 5. The system of claim 4 wherein the inflow microchannels andthe outflow microchannels are formed from flow paths etched in facingsurfaces of adjacent laminae.
 6. The system of claim 3 wherein themicrofluidic heat exchanger further comprises a heat transfer layerdisposed between a lamina of inflow microchannels and a lamina ofoutflow microchannels.
 7. The system of claim 3 wherein the inletcomprises an inlet opening extending through a plurality of laminae influid communication with the plurality of inflow microchannels in theplurality of laminae.
 8. The system of claim 3 wherein the microfluidicheat exchanger further comprises an outlet opening extending through aplurality of laminae and in fluid communication with the plurality ofoutflow microchannels in the plurality of laminae and with the mixer. 9.The system of claim 3 wherein the microfluidic heat exchanger furthercomprises a heater region in which the heater is disposed, the heaterregion being in fluid communication with a plurality of laminae.
 10. Thesystem of claim 2 wherein the microfluidic heat exchanger furthercomprises a residence chamber comprising a flow pathway downstream ofthe heater and upstream of the outflow microchannels.
 11. The system ofclaim 1 wherein the inlet microchannel and the outlet microchannel aredisposed in a counterflow arrangement.